Effect of modification of brain serotonin (5-HT), norepinephrine (NE) and dopamine (DA) on ethanol tolerance.
Rats were permanently depleted of brain dopamine (DA), serotonin (5-HT), 5-HT + norepinephrine (NE), or NE + DA by intraventricular injection of either 5,7-dihydroxytryptamine (5,7-DHT) or 6-hydroxydopamine (6-OHDA) with or without pretreatment with desmethylimipramine (DMI). Following 1 week of recovery from surgery, daily treatment with ethanol (5 g/kg, PO) or isocaloric sucrose was carried out for a period of 20-25 days. Testing at 5-day intervals showed that chronic ethanol treatment produced tolerance to the hypothermic and motor impairing effects of ethanol. Depletion of 5-HT alone retarded tolerance, while depletion of NE or DA alone produced no effect. Combined depletion of both NE and 5-HT, however, completely inhibited tolerance development. The inhibition of tolerance development by combined depletion of both NE and 5-HT is discussed in terms of a reciprocal relationship between these two systems.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000032:analysis*; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis*
D006892:Hydroxydopamines; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D000431:Ethanol; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine